Is NPHP3 p.Ala150Val (c.449C>T) pathogenic?

NPHP3 p.Ala150Val (c.449C>T) is classified Benign/Likely benign in NPHP3 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.3344); Low-frequency (popmax 2.2%, eas); Associated with kidney disorder.

What condition is associated with NPHP3 p.Ala150Val (c.449C>T)?

NPHP3 p.Ala150Val (c.449C>T) is associated with kidney disorder, renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome (ClinVar).

How common is NPHP3 p.Ala150Val (c.449C>T) in the general population?

NPHP3 p.Ala150Val (c.449C>T) is low-frequency (popmax 2.2%, eas) (gnomAD).

What do computational predictors say about NPHP3 p.Ala150Val (c.449C>T)?

AlphaMissense predicts likely benign (score 0.3344) — an in-silico prediction, not a clinical call.

NPHP3 p.Ala150Val

c.449C>T · rs142663818 · VCV241998

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.3344 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.2%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

kidney disorder

Computational evidence

Protein change
AlphaMissense	0.3344	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.5	GERP 0.97, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 30 kb · p 0.87 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.2% East Asian · 976/44,402 alleles

Filtering AF 2.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.04%

Overall 0.094% 1,504/1,599,856 alleles · low-frequency exomes 1,297/1,448,180 · genomes 207/151,676 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.2%	45
African / African-American	0.232%	432
Remaining individualsnot grpmax-eligible	0.167%	600
South Asian	0.122%	817
Ashkenazi Jewishnot grpmax-eligible	0.106%	944
Admixed American	0.0168%	5,949
Middle Eastern	0.0167%	5,996
European (non-Finnish)	0.00854%	11,711
Finnishnot grpmax-eligible	0.00158%	63,148

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NPHP3
Protein: p.Ala150Val
Coding: c.449C>T
MANE Select: NM_153240
dbSNP: rs142663818
Type: single nucleotide variant
Location: chr3:132719775 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.59 · 1 PDB

Full NPHP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal-hepatic-pancreatic dysplasia 1 NPHP3-related Meckel-like syndrome nephronophthisis 3 nephronophthisis

Similar variants

NPHP3 p.Ala150Gly Uncertain significance ★ ⚠ same residue
NPHP3 p.Ala150Thr Uncertain significance ★ ⚠ same residue
NPHP3 c.1985+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP3 c.3201+1G>T Likely pathogenic ★★ same condition
NPHP3 c.393+1G>C Likely pathogenic ★★ same condition
NPHP3 c.520-1G>T Pathogenic ★★ same condition
NPHP3 c.823+1G>T Likely pathogenic ★★ same condition
NPHP3 c.958-2A>G Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nphp3-p-ala150val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown